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We thoroughly enjoyed the Vatican Museum and the Sistine Chapel, mostly because there were few people while we were there on the Walks of Italy Pristine Sistine tour. We were able to sit on the benches in the Sistine Chapel and really take it all in. I do prefer seeing art in the churches or palaces for which it was created, but better to see it at a place like the Vatican Museum than not at all.

We were also in the Vatican courtyard in the late afternoon in May and the line into the Basilica was quite long. We were so glad we weren't in it!

Agree with drchris and since you cant talk in the Sistine, listening to the free audio guide from Rick Steeves on our ipod helped us to understand what we were actually looking at as we sat along the walls.

There is often a very long ticket queue for the
Vatican Museums, even in the afternoons, although it's less likely then. Inside the Museums, there is a short queue to exchange your voucher for a ticket, and another for security.

For the Basilica, there is often a very long security queue. It moves quickly, but you could sometimes still spend half an hour or more in line. This queue usually vanishes by late afternoon.

I myself would never go to the Vatican Museums in the summer; I did that once, and regretted it. I would also never again go on a weekend at any time of the year.

The Borghese Gallery is also often unpleasantly crowded to my taste. It's also not one of my favorite museums in Rome, partly because I'm not an admirer of Bernini. They often have good temporary exhibits, though, which I often attend. (This would be when it's unpleasantly crowded.)

There are many wonderful art museums in Rome, most of which are never crowded. The Barberini Gallery, mentioned by Pepper, is just one of these. I would also consider Palazzo Massimo alle Terme, the Musei Capitolini, the Corsini Gallery (which has a joint ticket with the Barberini Gallery), the Galleria Doria Pamphilj, the Villa Farnesina, and several others. None of these is ever overly crowded, and none require a reservation. All are easily reached from central Rome, many within easy walking distance from Piazza Venezia. Most cost less than €10.

The Scuderie del Quirinale, the Museo Vittoriano, and the Ara Pacis often have excellent temporary exhibits. The Palazzo Farnese and the Villa Medici, although not art museums, have regular visiting hours so you can admire their art collections. There are many churches that have world-famous art on display. For modern art, there are the the MACRO, the MAXXI, the Museo di Arte Moderna, and another with a similar name. These are just off the top of my head

All in all, I don't understand why most people consider the Vatican Museums and the Borghese Gallery to be the only two museums worth visiting in Rome.

Pepper-von-snoot
Let me rephrase that. Guards do yell silencio because you are supposed to be quiet in a Catholic church and out of respect for our church, we were quiet. Not sure how other religions handle that in their places of worship. The fact the guards had to do it frequently, only means there are people who may not be aware of that or don't follow that rule in their place of worship.